Metered dose delivery device for liquid and powder agents

ABSTRACT

A delivery device for the delivery of an agent to the mouth, nose or other bodily site of a user. The delivery device includes an aerosol canister that is actuated to expel propellant, which captures and disperses the agent. In a preferred embodiment, the propellant captures and disperses the agent into the mouth or nose of a user, and inhalation by the user directs the agent to the lungs of the user. The delivery device is particularly suitable for the treatment of bronchial asthma, respiratory conditions and for the delivery of systemically absorbed agents.

The present application claims the benefit of U.S. provisionalapplication No. 60/286,634, filed on Apr. 26, 2001, the teachings ofwhich are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to improved devices for the oral, nasal ortopical delivery of finely divided materials, such as medicinal agentsand drugs. More particularly, the present invention relates to a devicethat delivers medicament to the mouth or nose of a user by use of anaerosol canister housing a propellant.

BACKGROUND OF THE INVENTION

Certain disease of the respiratory tract are known to respond totreatment by the direct application of medicinal agents. As many suchagents are most readily available as a finely divided material, e.g., indry powdered form, their delivery is most conveniently accomplished byinhaling the finely divided material through the nose or mouth. Thisresults in better utilization of the medicinal agent in that it isdeposited exactly at the site desired and where its action may berequired; hence, very minute doses of the therapeutic agent are oftenequally as efficacious as larger doses administered by other means, witha consequent marked reduction in the incidence of undesired sideeffects. Alternately, the therapeutic agent in this form may be used fortreatment of diseases other than those of the respiratory system, forexample, for the delivery of systemically absorbed medicaments such asinsulin. When the drug is deposited on the very large surface areas ofthe respiratory tract, it may be very rapidly absorbed into the bloodstream; hence, this method of application may take the place ofadministration by injection, tablet, or other conventional means.

A variety of inhalation devices for the delivery of finely dividedmaterials are known in the art. For example, U.S. Pat. No. 4,240,418discloses inhalation devices wherein a container of finely dividedmaterial is positioned so that the material from the container can passby gravity to a delivery area of the device from which it is dispensed.Accordingly, these devices suffer the disadvantage that the use mustmaintain the device in a particular position so that the finely dividedmaterial can pass by gravity to the collecting plate and is notdislodged therefrom prior to dispensing. It appears that such devicesalso require a large dispensing passage to prevent interference with thefree fall of a relatively large load of the finely divided material.

Other known inhalation devices incorporate a deflector (U.S. Pat. No.4,098,273) or a hollow tube (U.S. Pat. No. 3,938,516) to divert air flowinto a chamber to dislodge the finely divided material, therebyrequiring a substantial flow of air to disperse the finely dividedmaterial. Inhalation sufficient to create such a substantial flow of airis difficult for some users, e.g., asthmatics. Furthermore, it isbelieved that such devices deliver somewhat imprecise doses due to theinevitable variations in residue of finely divided material left behindin the container after dispensing.

Some known inhalation devices use members which vibrate to dispense thefinely divided material, thus increasing the complexity and bulk of thedevice. For example, the devices of U.S. Pat. No. 3,948,264, utilizebatteries to activate vibrators. Other devices incorporate breathactivated vibratable members to disperse the finely divided materials.See, e.g., U.S. Pat. Nos. 3,888,253 and 4,995,385 which include a memberwhich vibrates in the airflow to dispense the finely divided material.Still other known devices use a breath activated propeller device tospin the container of finely divided material, thereby casting thematerial out by centrifugal force, e.g., U.S. Pat. No. 3,507,277. Arelatively high velocity of air flow is required to activate suchdevices, again a problem for breath impaired users.

Moisture in most powders tends to cause agglomeration and clumpingthereby inhibiting the breakup and dispersion of the finely dividedmedication, an essential step in effective dispensing of the material.However, the manner in which many known devices operate renders hermeticsealing of the container of finely divided material impossible. In stillother known devices, the containers for finely divided materials aregelatin capsules which are susceptible to atmospheric moisture.

Recently, inhalation devices have been developed which include anaerosol container housing a mixture of a propellant and a drug. See,e.g., U.S. Pat. Nos. 6,126,919, 6,120,752 and 6,054,488. Certain drugscannot be successfully mixed with propellants. Further, such mixturesoften result in agglomeration of the drug, degradation of thecomponents, chemical instability, and limited shelf lives. In an attemptto solve these problems, certain additives such as, for example,cosolvents, surfactants and dispersants are often added. As a result,pure medicinal agent is not delivered. Further, with such devices, priorto each use, it is required to shake the device vigorously to ensurethat the mixture of drug, cosolvents, surfactants, dispersants and othercomponents are suspended in the propellant and to try to provide auniform mixture of the components. Further, with such devices, it isimportant to keep track of how much medicine has been used so that theuser replaces the device before running out of the medicine. One waythis is done is for the user to write a refill date on the device. Tofigure out the refill date, a user must divide the number of puffs inthe device (often, this number is printed the device) by the number ofpuffs the user takes each day. The resulting number is the number ofdays the device should last. The user than counts forward that many daysto estimate the refill date. However, this process is inconvenient andis often inaccurate because it does not take into account days in whichmore or fewer puffs are taken.

New and more potent drugs which can be used in increasingly smallquantities are being developed on an ongoing basis. In most instances,known inhalation devices for finely divided materials are not capable ofdelivering such small quantities without the addition of a significantamount of filler. It is highly desirable to minimize the use of suchfillers, e.g., in order to reduce the likelihood of side effects.

It can be seen that presently known devices for the delivery of finelydivided materials suffer disadvantages which include, among others,imprecise delivery, inability to deliver directly from a hermeticallysealed container, agglomeration and clumping of the medicinal agents,reduced shelf life of the medicinal agents, chemical instability,inability to deliver small doses of pure medicinal agent, requirement ofgood coordination for use and high breath demands upon the user,requirement to shake the device to prevent settling of the medicinalagent, limited portability due to bulk, difficulty to keep track of howmuch medicinal agent has been used and how much remains and complexityof design. Thus, alternative inhalation devices are being sought.

SUMMARY OF THE INVENTION

The present invention provides a novel device for the oral or nasaldelivery of agents, such as medicinal agents and drugs, which reduces orovercomes many deficiencies of prior art devices. More particularly, thepresent invention relates to a device that delivers an agent to themouth or nose of a user by means of an aerosol canister housing apropellant. In particular, the present invention provides a device inwhich the agent and the propellant are kept separated, e.g. in separatecontainers or compartments, and combined at the instant of actuation.The delivery device may also provide beneficial effects for the deliveryof agents to other bodily sites including, for example, the eye and ear.

As used herein, a propellant includes both compressed and liquefiedgases. In some embodiments, however, liquefied gases, which requirelower pressures than compressed gasses to be liquefied, are preferableto compressed gases.

In an exemplary embodiment, the delivery device includes a body memberhaving an aerosol canister at a first end and a second end for insertioninto a user's mouth or nose. A container, housed within the body memberbetween the aerosol canister and the second end, contains an agent. Amechanism for exposing the agent in the container to the propellant isfurther included. In a preferred embodiment, the mechanism is a piercingmember, such as a needle or a blade, housed within the body memberbetween the aerosol canister and the container. Preferably, themechanism is movable within the body member and, during use, themechanism, e.g. piercing member or blade, is lined up with the agent inthe container and is moved towards and through the container. The agentis then delivered to the mouth or nose of a user by the propellant,which is expelled by actuation of the aerosol canister. The propellantcaptures and disperses the agent through the second end and into themouth or nose of the user. Preferably, the propellant is expelled with aforce adequate to cause substantially complete dispersion of the agent,and inhalation by the user directs the agent to the lungs of the user.

In a particularly preferred embodiment, the aerosol canister is movablewithin the body member and the mechanism is a piercing member inconnection with the aerosol canister such that, as the aerosol canisteris moved within the body member towards the container, the piercingmember, likewise, moves towards and through the container. As theaerosol canister moves towards and through the container, it preferablyencounters a stop or similar mechanism that actuates the aerosolcanister to expel propellant.

In yet another preferred embodiment, the mechanism is a piercing memberin the form of a needle having at least a hollow tip portion thatpierces and passes through the container. As the hollow tip portionpierces and passes through the container, the agent is picked up withinthe hollow portion of the piercing member and is carried towards thesecond end of the body member. Propellant, expelled from the aerosolcanister then forces the agent from the needle, through the second endand into the mouth or nose of a user.

Preferably, the piercing member is designed such that it issubstantially hollow along its length. As such, when the piercing memberis in line with the aerosol canister, propellant expelled from theaerosol canister passes through the hollow of the piercing member. Asthe propellant travels through the piercing member, it encounters theagent picked up within the piercing member and disperses the agent outof the piercing member into the mouth or nose of the user.

The hollow needle is not limited in its cross sectional shape and, forexample, it may have a circular, oval, square, triangular, or othercross sectional shape. In one preferred embodiment, the needle isdesigned such that the hollow portion is sized to accommodate and pickup a precise dose of agent. For example, the cross section of the hollowportion may be made larger or smaller to accommodate more or less agent.

Preferably, the hollow needle is sized such that the cross section ofthe needle is substantially the same as the cross section of the portionof the container housing the agent, so as to minimize any residue ofagent in the container.

In another preferred embodiment, the mechanism is a piercing member inthe form of a solid needle. In this embodiment, as the needle is movedthrough the container, it picks up the agent in the container and pushesthe agent through the container toward the second end of the bodymember. The agent is then delivered to the mouth or nose of a user bythe propellant, which is expelled by actuation of the aerosol canister.The propellant picks up and disperses the agent out of the second endand into the mouth or nose of the user. Preferably, the propellant isexpelled with adequate force to substantially completely disperse theagent, and inhalation by the user directs the agent to the lungs of theuser.

The solid needle is not limited in its cross sectional shape and it mayhave, for example, a circular, oval, square, triangular, or other crosssectional shape. Preferably, the solid needle is sized such that thecross section of the needle is substantially the same as the crosssection of the portion of the container housing the agent, so as tominimize any residue of agent in the container.

In embodiments where the solid needle is sized with a cross sectionsubstantially the same as the cross section of the portion of thecontainer housing the agent, bypass pathways are preferably included inthe device. For example, one or more bypass pathway may be formed aroundthe portion of the container housing the agent such that propellantexpelled from the aerosol canister passes through the one or more bypasspathway to the second end of the body member where the propellantcaptures and disperses the agent into the mouth or nose of the user. Thebypass pathways may also be included in other embodiments, for example,where the mechanism is a hollow needle.

In some embodiments of the present invention, the solid or hollow needlemay be sized with a cross section smaller than the cross section of theportion of the container housing the agent such that at least a portionof the propellant may be expelled through the portion of the containerhousing the agent around the needle. In this embodiment, the bypasspathways may also be included to allow for additional pathways throughwhich additional propellant can be expelled. Thus, the propellant may beexpelled both through the portion of the container housing the agent(e.g. around the needle and through the hollow needle) and through thebypass pathways.

In another embodiment, the piercing member is in the form of a bladehaving a cross section less than the cross section of the portion of thecontainer housing the agent. As the blade pierces the container, anopening through the container housing the agent is formed. Propellant isthen expelled around the blade and through the opening formed by theblade, thereby forcing the agent out of the container, through thesecond end and into the mouth or nose of a user. In one embodiment, theagent within the container is sealed at the top and/or bottom of thecontainer by a conventional piercable material such as, for example, aplastic or metal film, to ease piercing of the container and to enablefurther opening up of the container. Thus, as the propellant is forcedaround the blade through the opening formed by the blade, the force ofthe propellant against the piercable material surrounding the openingformed by the blade further opens up the piercable material and assistsin driving the agent out of the container. In this case, most if not allof the agent in the container will be expelled.

In this blade embodiment, bypass pathways may also be included to allowfor additional pathways through which additional propellant can beexpelled. Thus, the propellant may be expelled both through the portionof the container housing the agent around the blade and through thebypass pathways.

Preferably, the delivery device is designed to deliver precise doses ofagent. This may be accomplished by, for example, sizing the portion ofthe container housing the agent so as to accommodate a precise dose ofagent. For example, the thickness and/or cross-section of the containeror portion of the container holding the agent may be increased ordecreased to hold more or less agent. This may also be accomplished by,for example, sizing the hollow portion of the piercing member so as toaccommodate a particular dose of agent.

The present invention provides delivery devices and methods of use thatgreatly reduce and, in some instances, eliminate the problems associatedwith currently available delivery devices. For example, the presentdelivery devices and methods of use effectively deliver precise doses ofagents, prevent agglomeration and clumping of the medicinal agents, areeasy to use, require minimal inhalation by the user and are capable ofdelivering small amounts of medicaments without the use of fillers.

Still further, contrary to devices that mix the medicinal agent with apropellant in an aerosol canister, the present device does not requirethe agent to come into contact with the propellant until the point intime that the agent is administered. Thus, the agent may be provided insubstantially pure form. As a result, the chemical stability of theagent is not diminished by contact with a propellant and the shelf lifeof the agents is not diminished in this manner. Further, the device neednot be shaken well prior to use to prevent settling of the agent.

In preferred embodiments of the present invention, the agent is providedin containers housing individually sealed doses rather than providing abulk amount of agent mixed in a propellant. Thus, a user need not keeptrack of uses of the device to estimate how many doses of the medicinalagent remain in the device as with conventional aerosol deliverydevices. A user of the present device merely uses the device andreplaces the container housing the agent between each use with singledose containers. Alternatively, with multiple dose containers having aplurality of compartments each housing a single dose, a user merelyneeds to look at the container to see how many compartments have beenpierced to see how many doses have been used and how many doses remain.Thus, the potential for erroneously estimating the number of dosesremaining is eliminated and a user can eliminate the danger of carryinga delivery device with no remaining doses or fewer doses than believed.

Other aspects and embodiments of the invention are discussed below.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side cross-sectional view of one embodiment of the deliverydevice in accordance with the present invention.

FIG. 2 is an enlarged side cross-sectional view of the piercing memberand container portions of the delivery device shown in FIG. 1.

FIG. 3 is a view of the aerosol container within the delivery device ofFIG. 1.

FIG. 4 is a cross-sectional view of the components inside the bodymember in accordance with another embodiment of the delivery devicewherein the delivery device includes a plurality of bypass channels.

FIG. 5 is an enlarged cross-sectional view of FIG. 4 excluding theaerosol canister.

FIG. 6 shows a view of the device shown in FIG. 5 taken along line A-A.

FIG. 7 is a side cross-sectional view of the components inside the bodymember in accordance with another embodiment of the delivery devicewherein the delivery device includes a plurality of bypass channels andwherein the device is shown with the top portion separated from thebottom portion.

FIG. 8 a is an enlarged view of the top and bottom portions of thedevice shown in FIG. 7.

FIG. 8 b is an enlarged view of a holding member for holding thecontainer of agent in accordance with one embodiment of the presentinvention.

FIG. 8 c is an enlarged view of a holding member having grooves and acontainer having protrusions in accordance with one embodiment of thepresent invention, wherein the grooves in the holding member andprotrusions in the container correspond to each other when the containeris properly inserted in the holding member.

FIG. 8 d is an enlarged view of a holding member having protrusions anda container having grooves in accordance with one embodiment of thepresent invention, wherein the grooves in the holding member andprotrusions in the container correspond to each other when the containeris properly inserted in the holding member.

FIG. 9 is a cross-sectional view of the components inside the bodymember in accordance with another embodiment of the delivery devicewherein the delivery device includes an expansion chamber.

FIG. 10 is an enlarged view of the device shown in FIG. 9.

FIG. 11 a shows an enlarged view of the container having a single centercompartment housing the agent.

FIG. 11 b shows an enlarged view of the container having a plurality ofcompartments housing the agent.

FIG. 12 a shows views of another embodiment of the present invention,wherein the container is elongate and can be slid into and out of a slotin the device, like a drawer.

FIG. 12 b shows an upper enlarged view of an elongate container inaccordance with one embodiment of the present invention.

FIG. 12 c shows a side enlarged view of an elongate container inaccordance with one embodiment of the present invention.

FIG. 13 a shows a view of another embodiment of the present invention,wherein a drawer-like holding member holds the container of agent andwherein the drawer-like holding member can be slid into and out of aslot in the device.

FIG. 13 b shows an upper enlarged view of a drawer-like holding memberin accordance with one embodiment of the present invention.

FIG. 13 c shows a side enlarged view of a drawer-like holding member inaccordance with one embodiment of the present invention.

FIG. 14 a shows a view of another embodiment of the present invention,wherein an elongate container that can be slid into and out of a slot inthe device, like a drawer, is stabilized by a vertical stabilizingmember.

FIG. 14 b shows a view of another embodiment of the present invention,wherein an elongate container that can be slid into and out of a slot inthe device, like a drawer, is stabilized by one or more horizontalstabilizing members.

FIG. 15 a shows an enlarged view of another embodiment of the presentinvention wherein the mechanism for exposing the agent in the containerto the propellant is the valve stem and wherein a stop member or coveris used to form a channel through which the propellant is directedthrough the container.

FIG. 15 b shows FIG. 15 a without the container or valve stem in place.

FIG. 16 a-b show embodiments of the piercing member passing through thecompartment in the container while providing clearance between thepiercing member and one or both sides of the compartment.

FIG. 17 a shows another embodiment of the delivery device of the presentinvention wherein the device includes a guiding mechanism that guidesthe piercing member through a precise location in the container, whereinthe guiding mechanism is in the form of one or more pins andcorresponding grooves that line up when the piercing member is preciselyaligned with the desired location in the container.

FIG. 17 b shows an enlarged view of the guiding mechanism of FIG. 17 a.

FIG. 18 a shows another embodiment of the delivery device of the presentinvention wherein the second end of the device is enlarged or flared.

FIGS. 18 b-e show the steps of using the delivery device in accordancewith another embodiment of the present invention.

FIG. 19 shows the “black box” used in the Examples.

FIG. 20 a shows a cross-section side view of another embodiment of thedelivery device of the present invention wherein the device includes aguide mechanism that guides the piercing member through a preciselocation in a drawer-like holding member including the container for theagent, wherein the guiding mechanism is in the form of one or more pinsand corresponding holes and grooves that line up when the piercingmember is precisely aligned with the desired location in relation to thecontainer.

FIG. 20 b shows a top view of the drawer-like holding member of FIG. 20a.

FIG. 20 c is an enlarged cross-section view of the device of FIG. 20 ain the discharge position wherein the needle has passed through thecontainer in the drawer-like member and is stopped at the top of acurved section adjacent to the nozzle.

FIG. 21 a is an exploded cross-section front view of the device shown inFIG. 20, showing guide pins and apertures for accepting the pins.

FIG. 21 b is a cross-section front view of the device shown in FIG. 20in the discharge position, wherein the needle has passed through thecontainer and stopped.

DETAILED DESCRIPTION OF THE INVENTION

Although the delivery devices of the present invention are primarilyillustrated and described herein by means of devices which have beenadapted for oral delivery, it will be appreciated by those skilled inthe art that such devices may also be adapted for nasal and other bodilysite delivery. Further, although the devices of the present inventionare primarily illustrated and described herein by means of deviceshaving a mechanism in the form of a piercing member, particularly ahollow needle, it will be appreciated by those skilled in the art thatsuch devices may also be adapted having other forms of mechanisms suchas solid needles and blades.

Referring now to the various figures of the drawing, wherein likereference characters refer to like parts, there is shown in FIGS. 1-18evarious views of a delivery device 1, in accordance with the invention.

As shown in FIG. 1, the delivery device 1 includes a body member 2having a first end 4 and a second end 6. An aerosol canister 8, housinga propellant, is located at the first end 4 of the body member 2. Thesecond end 6 is designed for insertion into a user's mouth or nose. Acontainer 10, which contains an agent, is further housed within the bodymember 2 between the aerosol canister 8 and the second end 6. Thedelivery device further includes a mechanism for exposing the agent inthe container 10 to the propellant. In a preferred embodiment, themechanism is a piercing member 12, such as a needle or blade, preferablypositioned within the body member 2, between the container 10 and theaerosol canister 8. The piercing member 12 is movable within the bodymember 2 and may be moved so as to pierce and pass through the container10. The agent within the container 10 is delivered to the mouth or noseof a user by actuation of the aerosol canister 8. Actuation of theaerosol canister 10 expels the propellant from the aerosol canister 10towards the agent and disperses the agent out of a nozzle 27 into thesecond end 6 and into the mouth or nose of the user.

The body member 2 may be any convenient shape. As shown in FIG. 1, thebody member 2 may be formed of an upper portion 14 and a lower portion16 extending at an angle from the bottom of the upper portion 14 as isconventional in the art. For example, conventional devices have beenformed with an angle between the upper and lower portions ranging fromabout 110° to about 115°. Such an angled arrangement has been found toassist in directing the propellant and agent to the desired treatmentlocation and makes it easier to comfortably use of the device. Ofcourse, the shape of the body member 2 is not limited to such anarrangement, and other body member 2 shapes may be used.

In a preferred embodiment, the lower portion 16 extends at an angle fromthe upper portion 14 and is connected to the upper portion 14 via hingesor other fastening means 18 such as, for example, corresponding threadedportions on the upper portion 14 and lower portion 16, that allow thelower portion 16 to be separated from the upper portion 14. Any othertype of mechanism that is useful in providing access to the interior ofthe body member 2 and/or to allow for easy insertion and removal of thecontainer 10 housed within the body member 2 may be used.

In the embodiment shown in FIGS. 1 and 2, a holding member 20 is mountedwithin the body member 2 for holding the container 10 in place withinthe device. For example, the holding member 20 may be mounted in thelower portion 16, as shown in FIG. 1, such that as the lower portion 16of the body member 2 is separated from the upper portion 14, forexample, by swinging the lower portion 16 open along hinges or otherfastening means 18, the holding member 20, likewise, swings along withthe lower portion 16 and easy access is provided to remove and replacethe container 10.

The container 10 may be any convenient shape. In the embodiments shownin FIGS. 6 and 11 a-b, the container 10 is cylindrical. In theembodiment shown in FIGS. 12 a-c, the container 10 is elongate.Furthermore, the container 10 may be single or multicompartmental.

In the embodiment shown in FIG. 1, the holding member 20 is designed tosecurely hold the container 10 and prevent vertical, horizontal androtational movement of the container 10 during use. Thus, for example,the holding member 20 may be designed to have an opening 34, as shown inFIG. 8 b, that is sized and shaped to snugly fit the container 10. Insome embodiments, the container 10 has a snap fit within the opening 34of the holding member 20. In some embodiments, the holding member 20 hasan opening 34 that includes one or more protrusions 35 or grooves 37that correspond to one or more grooves 36 or protrusions 38 in thecontainer 10, so that the container 10 is placed into the opening 34with the grooves 36 or protrusions 38 of the container 10 engaging theprotrusions 35 or grooves 37 in the opening 34 of the holding member 20,as shown, for example, in FIGS. 8 c-d.

The container 10 and holding member 20 are preferably sized and shapedsuch that when the container 10 is inserted into the opening 34 of theholding member 20, the container 10 is automatically positioned in linewith the aerosol canister 8 and the piercing member 12 or othermechanism. In preferred embodiments, the container 10 is designed suchthat it is symmetrical left to right and top to bottom, for example, asshown in FIGS. 11 a-b, so that the container 10 can be quickly andeasily inserted into the opening 34 left end first, right end first,facing up or facing down. Alternatively, the container 10 may bedesigned so that it is, for example, properly inserted facing up, forexample, as shown in FIGS. 8 c-d. To ensure proper insertion, the topend could, for example, be enlarged to a size larger than the opening 10so that the container 10 could not be inserted facing down because itwould not fit. Another way to ensure proper insertion could be toinclude some type of indicia on the container 10, such as an arrow,indicating the proper direction of insertion.

In another embodiment, a drawer-like or similar mechanism 40 may beincluded in the body member 2 such that the drawer-like or similarmechanism may be, for example, pulled out or swung open, therebyproviding access to the interior of the body member for insertion andreplacement of the container 10. In one preferred embodiment, forexample, as shown in FIG. 13, the drawer 40 may be pulled in and out ofthe body member 2 such that when the drawer 40 is pulled out, the drawer40 has a bottom surface that is designed as a holding mechanism on whichthe container 10 is placed and when the drawer 40 is pushed back insidethe body member, the container 10 is positioned for use. Preferably, aswith the holding member 20, the drawer-like or similar mechanism 40 isdesigned to securely hold the container 10 and prevent vertical,horizontal and rotational movement of the container 10 during use. Thus,the drawer-like or similar mechanism 40 may, like the holding member, 20include an opening 42 like that described above for the holding member20. The container 10 and drawer-like or similar mechanism 40 arepreferably sized and shaped such that when the container 10 is insertedinto the drawer-like or similar mechanism 40, the container 10 isautomatically positioned in line with the aerosol canister 8 and thepiercing member 12 or other mechanism. In preferred embodiments, thecontainer 10 is designed such that it is symmetrical left to right andtop to bottom so that the container 10 can be quickly and easilyinserted into the drawer-like or similar mechanism 40 left end first,right end first, facing up or facing down. Alternatively, the container10 may be designed so that it is, for example, properly inserted facingup. To ensure proper insertion, the top end could, for example, beenlarged to a size larger than the opening 42 in the drawer-like orsimilar mechanism 40 so that the container 10 could not be insertedfacing down because it would not fit. Another way to ensure properinsertion could be to include some type of indicia on the container 10,such as an arrow, indicating the proper direction of insertion. In someembodiments, one or more stabilizing members 46 are positioned withinthe body ember 2, for example, as shown in FIG. 13 a and 14 b, on and/orbetween which the drawer-like or similar mechanism 40 can rest wheninserted in the device to prevent the drawer-like or similar mechanism40 from vertical movement during use. For example, as shown in FIG. 13a, a vertically extending stabilizing member 46 is positioned such thatthe drawer 40, when inserted, rests on the stabilizing member 46 andprevents vertical movement. In another embodiment, as shown in FIG. 14b, one or more horizontally extending stabilizing members 46 can belocated about the slot 44 such that the drawer 40 or elongate container10, when inserted rests on or between the one or more horizontallyextending stabilizing members 46. These stabilizing members 46 canextend along a portion of the drawer 40 length, for example, as shown inFIG. 14 b or along the entire drawer 40 length, for example, as shown inFIG. 14 c. When the stabilizing member(s) 46 extend along thecompartment 22 of the container 10 that houses the agent, a lumen 48 islocated in the stabilizing member(s) 46 through which the piercingmember 12, propellant and agent may pass, for example, as shown in FIG.14 a. The horizontally extending stabilizing members 46 prevent thedrawer-like or similar mechanism 40 from horizontal movement during use.

In yet another preferred embodiment, rather than provide a drawer-likeor similar mechanism 40 for holding the container 10, a slot 44 islocated in the body member 2 and the container 10 is designed to slidein and out of the slot 44 much like a drawer. For example, as shown inFIGS. 12 a-c, the container 10 can be elongate in shape, like a drawer,and the slot 44 is sized and shaped in accordance with the size andshape of the container 10 so that the container 10, when inserted intothe slot 44, is held securely and is prevented from vertical, horizontaland rotational movement within the slot 44. The container 10 ispreferably sized and shaped such that when it is inserted into the slot44, it is automatically positioned in line with the aerosol canister 8and the piercing member 12 or other mechanism. For example, as shown inFIGS. 14 a-b, the container 10 may be elongate in shape, and insertedinto the slot 44 such that at least a portion of one end of thecontainer 10 remains external to the slot or opening for easy removaland replacement. In preferred embodiments, the container 10 is designedsuch that it is symmetrical left to right and top to bottom so that thecontainer 10 can be quickly and easily inserted left end first, rightend first, facing up or facing down. Alternatively, the container 10 maybe designed so that it is properly inserted left end first. To ensureproper insertion, the right end could be enlarged to a size larger thanthe slot or opening so that the container 10 could not be inserted rightend first because it would not fit. Another way to ensure properinsertion could be to include some type of indicia on the container 10,such as an arrow, indicating the proper direction of insertion. Further,the container 10 could also be designed such that it is properlyinserted facing up. Likewise, the container may be sized to preventinsertion with the container 10 facing down or could include some typeof indicia on the container that indicates proper direction ofinsertion. As with the drawer-like or similar mechanism 40, when thecontainer 10 is in the form of a drawer that is slid into and out of aslot 44, one or more stabilizing members 46 are preferably positionedwithin the body member 2, for example, as shown in FIG. 14 a-b, onand/or between which the container 10 can rest when inserted in thedevice to prevent the container 10 from vertical movement during use.For example, as shown in FIG. 14 a, a vertically extending stabilizingmember 46 is positioned such that the container 10, when inserted, restson the stabilizing member 46 and prevents vertical movement. In anotherembodiment, as shown in FIG. 14 b, one or more horizontally extendingstabilizing members 46 can be located about the slot 44 such that thecontainer 10, when inserted rests on or between the one or morehorizontally extending stabilizing members 46, which prevent thedrawer-like or similar mechanism 40 from horizontal movement during use.These stabilizing members 46 can extend along a portion of the container10 length, for example, as shown in FIG. 14 b or along the entire drawer40 length, for example, as shown in FIGS. 2, 7, 8 a-d, 13 a, 14 b and 15a-b. When the stabilizing member(s) 46 extend along the compartment 22of the container 10 that houses the agent, a lumen 48 is located in thestabilizing member(s) 46 through which the piercing member 12,propellant and agent may pass, for example, as shown in FIG. 14 a.

The container 10, which houses an agent, is located within the bodymember 2 between the aerosol canister 8 and the second end 6. Thecontainer 10 has a top end 11 and bottom end 13, and the container 10 ishoused within the body member 2 such that the piercing member 12 passesthrough the top end 11 then the bottom end 13 as it pierces and passesthrough the container 10.

In one embodiment, as best shown in FIG. 8, 11 a and 11 b, the container10 has one or more compartments 22, 22 a that house the agent. The oneor more compartments 22, 22 a are depicted as cylindrical in shape.However, the shape of the one or more compartments 22, 22 a is notparticularly limited in shape.

For example, in one embodiment, as shown in FIGS. 8 and 11 a, thecontainer 10 may be cylindrical in shape and have a singe centercompartment 22 a housing the agent. In this embodiment, the container 10is positioned within the body member 2 such that the center compartment22 a is directly in line with the path of travel of the piercing member12. However, the portion of the container 10 housing the agent need notbe in the center of the container 10 as long as the compartment 22, 22 acontaining the agent is in line with the path of travel of the piercingmember 12.

In another embodiment, as shown in FIG. 11 b, rather than having asingle center compartment 22 a of the container 10 housing the agent, aplurality of compartments 22 within the medicament container 10 maycontain the agent such that a single container 10 may contain aplurality of doses of agent. Thus, containers 10 of a given size cancontain different numbers of single doses depending upon therequirements of the particular agent in use. Thus, one inhalation devicein accordance with the present invention can have many differentapplications.

The container 10 having a plurality of compartments 22 is preferablymounted within the body member 2 so that the container 10 may be rotatedor positioned to line up each of the compartments 22 with the piercingmember 12. For example, in one embodiment, the container 10 is disk-likein shape with the plurality of compartments 22 positioned in a circle,see FIG. 11 b. In this embodiment, the container 10 is preferablyrotatably mounted in the body member 2 to allow for a user to line upeach compartment 22 with the piercing member 12 by simple rotation ofthe compartment 10. As such, for example, the container 10 may berotatably, centrally disposed on a pin or similar mechanism (not shown).The container 10 may further be provided with a conventional lockingmeans (not shown) so that during rotation, the container 10 is locked inposition each time a compartment 22 is disposed in line with the path oftravel of the piercing member 12, thereby locating each single dose fordispensation. The container 10 can be rotated mechanically or,alternatively, may be rotated by hand. Alternative designs for themedicament container 10 may also be used, such as, for example, multiplecompartment strips, either rigid or in flexible rolls, e.g., as in acartridge belt for an automatic weapon, and so forth. For embodimentswherein the container 10 is in the form of an elongate drawer that isslid into and out of a slot 44 into position, a plurality ofcompartments 22 can be arranged in a line and the container 10 slid intothe slot at varying depths for delivery of agent from each compartment22. In this embodiment, the container 10 is preferably provided with aconventional locking means (not shown) so that as the container 10 isslid into the slot 44, the container 10 is locked in position each timea compartment 22 is disposed in line with the path of travel of thepiercing member 12, thereby locating each single dose for dispensation.

Alternatively, rather than using one or more compartments 22, 22 a ofthe container 10 housing the agent, the entire container 10 may behollow and may house the agent if desired.

The container 10 is typically made of conventional molded plastics, suchas acrylic, polypropylene, polyethylene, acetal, ABS and so forth.However, other conventional materials known to those skilled in the artmay also be used.

In one embodiment, the portion of the container 10 housing the agent maybe sized so as to provide a precise dose of agent to a user. Forexample, in one embodiment, the agent is housed within one or morecompartments 22, 22 a having a particular diameter and/or height. As thediameter and/or height of the compartment(s) 22, 22 a increase, moreagent may be contained within the compartment(s) 22, 22 a.

Compartment(s) 22, 22 a for use in the present invention may be sealedat the top end 11 and bottom end 13 with a conventional piercablematerial using methods known to those skilled in the art. In suchembodiments, the thickness of the piercable material is preferably nogreater than about 0.004 inch, more preferably, between about 0.001 andabout 0.003 inch, and more preferably, between about 0.001 and about0.0015 inch. The desired characteristics for such piercable materialsare high tensile strength to avoid tearing during perforation andresistance to the passage of moisture. In one preferred embodiment, apolyester film having heat activating adhesive on one side is used toseal the container 10. Although polyester is preferred, other filmsknown in the art, such as aluminum foil, polyolefin and polypropylenemay also be employed. In a particularly preferred embodiment, alamination of aluminum foil and a high tensile strength material, suchas a plastic film, is used. For example, the seal may be a multilayeredseal fabricated of one or more layers of aluminum foil and one or morelayers of polyester, polyolefin and/or polypropylene film. In suchembodiments, the aluminum foil layer(s) provide a barrier that protectsthe agent within the container from moisture and other external elementsand the plastic layer(s) provide additional strength to preventinadvertent piercing of the easily piercable aluminum layer and alsoassists in preventing the seal from becoming completely detached fromthe container as the piercing member 12 passes through the seal. Forexample, in one embodiment, the outermost layer is an aluminum foillayer, followed by an inner polyester layer laminated on the aluminumfoil layer. A heat activating adhesive on the polyester layer securesthe seal to the container 10. Alternatively, the entire container 10 orthe entire top end 11 and bottom end 13 of the container 10 may befabricated of a piercable material.

In the manufacture of such embodiments, the container 10 is typicallyfirst sealed on one side 11 or 13 with the piercable sealing material.The agent is then added to the container 10 and the container 10 is thenhermetically sealed by sealing the other side 11 or 13 of the container10 with the piercable sealing material.

The agent may comprise a single type of component or a blend ofcomponents. Preferably, the agent is selected from one or more medicinalagents and drugs. If desired, the agent may further comprise flavoringagents, surfactants, water, alcohol or other solvents provided that suchadditives are compatible with the agents and do not adversely impactstability.

The agent may be in the form of a liquid or in the form of finelydivided particles. In one embodiment, the agent is in the form of finelydivided particles having diameters ranging from about 1 micron to about50 microns, more preferably, from about 2 microns to about 50 microns.In some embodiments, the agent can, for example, be dissolved in wateror another solvent in which the agent is stable to dilute the dose ofagent if, for example, the agent is a medicament that must beadministered at very low doses. Alternatively, the agent could bedispersed in a material (e.g. a powder or particulate material) in whichthe agent is stable to dilute the dose of agent.

Preferably, the agent is provided in a pharmaceutically effective amountfor the particular condition that the device is utilized for. Forexample, in one embodiment, the device is utilized to treat respiratoryconditions such as bronchial asthma, and the agent is provided in a dosethat ranges from about 5 μg to about 30 mg, more preferably, from about10 μg to about 20 mg.

The device of the present invention can be used to deliver a variety ofagents that can be used to systemically treat a variety of conditions.By way of example, some conditions that the device can be used to treatinclude, but are not limited to bronchial asthma, diabetes and cysticfibrosis. As such, the agent can include a variety of agents utilized totreat these conditions. For example, some conventional agents used totreat bronchial asthma include Albuterol, Serevent, Flovent, Ventolin,Singulair, Missing, Azmacort, Pulmicort, Accolate, Proventil andAtrovent. Any agents used to treat these and other conditionssystemically can be used with the present invention.

In one embodiment, the agent may comprise two or more components housedwithin the container 10 as a blend. However, by blending certaincomponents together, the shelf-life of the blend may, in some cases, bereduced. Thus, in another embodiment, where it is desirable to deliverthe blend of components in one application or blast of propellant, it ispreferred to provide a container 10 wherein the two or more agents areseparated from each other until use. For example, this may beaccomplished by providing a container 10 with layers of the agentsseparated by, for example, piercable material. Thus, in one embodiment,the container 10 has at its bottom end 13 a layer of piercable material,then a layer of an agent, then another layer of piercable material, thena layer of another agent, and so on, finally sealed at the top end 11with a layer of piercable material. In such an embodiment, as thepiercing member 12 passes through the container 10, it pierces thepiercable material at the top end 11, passes through a first agent,pierces another layer of piercable material, passes through a secondagent, and so on until the piercing member 12 exits the container 10through the piercable material at the bottom end 13. The propellant thenis expelled to capture the plurality of agents and deliver the blend ofagents to the user.

In the manufacture of such embodiments, the container 10 is typicallyfirst sealed on one side 11 or 13 with a piercable sealing material. Thefirst agent is then added to the container 10. A layer of piercablematerial then seals off the first agent. A second agent is then added tothe container followed by another layer of piercable material. When eachof the desired agents is added to the container 10, the container 10 isthen hermetically sealed by sealing the other side 11 or 13 of thecontainer 10 with a piercable sealing material.

The mechanism for exposing the agent in the container 10 to thepropellant is shown in the various Figures in the form of a piercingmember 12, particularly a needle or a blade. However, the mechanism isnot particularly limited to such forms provided it is capable ofallowing for the agent in the container 10, which is sealed, to beexposed to the propellant, released from the container 10 and carriedout of the second end 6 of the body member 2 by the propellant into themouth or nose of a user.

In one embodiment, mechanism is a piercing member 12 in the form of aneedle having at least a hollow tip portion. As the needle pierces andpasses through the container 10, the agent in the container 10 is pickedup within the hollow portion of the needle and is carried towards thesecond end 6 of the body member 2. Propellant expelled from the aerosolcanister then forces the agent from the needle, through the second endand into the mouth or nose of a user or to other bodily sites.

Preferably, the needle is substantially hollow along its length and isin line with the aerosol canister 8 such that propellant expelled fromthe aerosol canister 8 travels through the inside of the needle. As thepropellant travels through the needle, it contacts and carries the agentwithin the needle out of the needle, through the second end and into themouth or nose of the user.

The needle may be designed such that the hollow portion is sized and/orshaped so as to provide a precise dose of agent to a user. For example,the hollow portion may be sized and/or shaped to accommodate and pick upa precise dose of agent. Thus, for example, the diameter of the hollowportion of the needle may be made larger or smaller to accommodate moreor less agent as the needle pierces and passes through the container 10.

The needle is not limited in its cross sectional shape and, for example,it may have a circular, oval, square, triangular, or other crosssectional shape. Preferably, the needle has a cross sectionsubstantially the same as the cross section of the portion of thecontainer housing the agent, so as to minimize any residue of agent inthe container 10.

In one preferred embodiment, the inner diameter of the hollow needleranges from about 0.005″to about 0.1″, more preferably, from about 0.01″to about 0.08″. Of course, if the needle is not circular, the largestdimension of the cross section can be used to approximate the meandiameter for this purpose.

In another embodiment, the mechanism is a piercing member 12 in the formof a solid needle. In this embodiment, as the needle is moved throughthe container, it pierces the container 10 so as to provide a passagewaythrough which propellant from the aerosol canister 8 may be expelled.Preferably, the solid needle is designed push the agent through and outof the container 10 as it passes through the container 10. The agent isthen delivered to the mouth or nose of a user by the propellant, whichis expelled from the aerosol canister 8 by actuation of the aerosolcanister 8. The propellant passes around the solid needle, captures theagent, and carries the agent out of the second end and into the mouth ornose of a user. Preferably, the propellant is expelled with adequateforce to cause substantially complete dispersion of the agent, andinhalation by the user directs the agent to the lungs of the user.

The solid needle is not limited in its cross sectional shape and, forexample, it may have a circular, oval, square, triangular, or othercross sectional shape. In one embodiment, the needle has a cross sectionsubstantially the same as the cross section of the portion of thecontainer 10 housing the agent, so as to minimize any residue of agentin the container 10. As such, the propellant expelled from the aerosolcanister 8 may pass through the container 10 around the needle tocapture and disperse the agent to the mouth or nose of a user. Toprovide greater passageway through which the propellant may pass tocapture and disperse the agent, one or more bypass pathways 15 mayfurther be formed through which propellant from the aerosol canister 8may travel. For example, one or more bypass pathways 15 may be situatedso as to direct propellant from the aerosol canister 8 towards thesecond end 6 of the body member 2 where the needle pushes the agent fromthe container 10. The propellant, thus, travels through the one or morebypass pathways 15 to the second end where it meets up with the agentfrom the container and disperses the agent into the mouth or nose of auser.

Alternatively, the needle may be sized with a cross section smaller thanthe cross section of the portion of the container 10 housing the agentsuch that the propellant may be expelled through the portion of thecontainer housing the agent around the outer surface of the needle. Inthis embodiment, the one or more bypass pathways 15 may also be usedprovide additional space through which propellant may travel. Thus, thepropellant may be expelled both around the outer surface of the needleand through the one or more bypass pathways 15.

In another embodiment, the mechanism is a piercing member 12 in the formof a blade having a cross section less than the cross section of theportion of the container 10 housing the agent. As the blade pierces thecontainer 10, an opening is formed. Aerosol is then expelled around theouter surface of the blade and through the opening formed by the blade,thereby carrying the agent out of the container 10, through the secondend and into the mouth or nose of a user.

In one embodiment, the agent within the container 10 is sealed at thetop and/or bottom of the container 10 by a conventional piercablematerial such as, for example, a plastic or metal film or combinationsof plastic and metal films as described above, to ease piercing of thecontainer 10 and to enable further opening up of the opening formed bythe blade in the container 10. Thus, as the propellant is forced aroundthe blade through the opening formed by the blade, the force of thepropellant against the piercable material surrounding the openingfurther opens up the piercable material and assists in carrying theagent out of the container 10. This embodiment is not limited to usewith the blade and, for example, in any embodiment wherein the piercingmember 12 is smaller in cross section than the cross section of theportion of the container 10 housing the agent, the container may besealed with a piercable material or the like that promotes furtheropening up of the opening formed by the piercing member 12 in thecontainer 10.

The blade is not limited in cross sectional shape and it may, forexample, have an “X”-shaped, “T”-shaped, “U”-shaped or linear shapedcross section to provide openings in the form of an “X”, a “T”, a “U” ora slit, respectively. It is believed that any of these blade shapes willprovide an opening wherein pressure of the propellant expelled from theaerosol canister 8 will have a tendency to further open up the openingformed by the blade to facilitate escape of the agent out of thecontainer 10.

The piercing member 12 is preferably designed to avoid cutting a pieceof the container 10 or piercable material free as it pierces and passesthrough the container 10, thereby preventing ingestion of the container10 or piercable material. This may be accomplished by, for example,providing a piercing member 12 that is sharpened at the piercing end toabout a 30° to 60° angle and blunted at the rim of the piercing member12 opposite the apex of the point. With such an arrangement, thepiercing member 12 leaves the pierced portion of the container 10 orpiercable material “hinged” to the container 10. This can further beaccomplished by fabricating the piercable material of one or more layersof aluminum foil and one or more layers of polyester, polyolefin and/orpolypropylene film as set out above. In such embodiments, the plasticlayer(s) assists in preventing the seal from becoming completelydetached from the container as the piercing member 12 passes through theseal. Rather, with such an arrangement, the piercing member 12 leavesthe piercable material “hinged” to the container 10. Further, in someembodiments, by forming the piercing member 12 smaller than the crosssection of the portion of the container housing the agent and smallerthan the piercable material sealing the portion of the container 10housing the agent, the piercable material is further prevented frombecoming cut free as the piercing member 12 pierces and passes throughthe container 10.

In each of the embodiments of the piercing member 12, it may bedesirable to include one or more bypass pathways 15 situated so as todivert a portion of the propellant around the piercing member 12 andaround the portion of the container 10 housing the agent. Thus, forexample, a portion of the propellant expelled from the aerosol canistermay pass through the piercing member 12 and/or around the outer surfaceof the piercing member 12 through the portion of the container housingthe agent, and a portion of the propellant may pass through the one ormore bypass pathways 15. The bypass pathways 15 in conjunction with thepropellant passing through and/or around the piercing member 12, thenexpel the propellant towards the second end 6 where the propellant cancapture the agent from the container 10 and assist in dispersing theagent into the mouth or nose of a user. Such bypass pathways 15 areshown, for example, in FIGS. 4-8.

In a preferred embodiment, the bypass pathways 15 are included indelivery devices wherein the piercing member 12 is in the form of ahollow needle. Preferably, in embodiments wherein the inner diameter ofthe hollow needle is smaller than the size of the portion of the aerosolcanister 8 through which the propellant is expelled (e.g. the valve stem13), the propellant expelled from the aerosol canister 8 may be inexcess of the amount that can pass through the hollow needle at a giventime. This may cause backup of the propellant and a reduction in theforce of the propellant as it passes from the aerosol canister throughthe device. In this embodiment, inclusion of the one or more bypasspathways 15 provides additional areas through which the propellant fromthe aerosol canister 8 may pass, thereby eliminating backup of thepropellant at the needle and eliminating reduction in the force of thepropellant as it passes from the aerosol canister 8 through the deviceand out of the second end 6. Inclusion of the bypass pathways 15 may beadvantageous in certain embodiments where it is desirable to utilizehollow needles with small diameters, for example, where it is desirableto deliver a small does of agent and the size of the hollow needledetermines the size of the dose delivered.

In an alternative embodiment, the mechanism for exposing the agent inthe container to the propellant is the force of the propellant againstthe sealed container 10. In some embodiments, the device is designedsuch that the force of the propellant against the sealed containerremoves or opens the seal on the container 10, thereby releasing theagent from the container 10 and carrying the agent out of the second end6. In one embodiment, for example, the propellant would be expelled tohit the container 10, thereby causing the seal to open. The propellantwould then force the agent through the container 10 and through the sealat the bottom of the container 10. Preferably, a channel 50 or similarsealing mechanism, such as that shown in FIG. 15, would be included thatextends from the aerosol canister 8 directly to the surface of thesealed container 10. This channel 50 would preferably be formed so thatthe propellant is directed solely through the container 10 to preventthe propellant from opening the sealed container 10 and allowing theagent to flow upwards out of the container 10 towards the aerosolcanister rather than through the container 10 towards the second end 6to the user. One such embodiment is shown, for example, in FIG. 15,wherein the channel 50 is formed between the holding member 20 and astop block or cover 52 that is placed over the container 10 and holdingmember 20. The formation of the channel 50 is not limited to thisembodiment and other means of forming channels 50 could be used. Thechannel 50 is sized to precisely surround the portion of the container10 housing the agent and is positioned directly against the surface ofthe container 10 to provide a sealed pathway from the aerosol canisterto the container 10. This channel 50, in some embodiments, couldcomprise the valve stem 13 of the aerosol canister 8. When the valvestem comprises the channel, the valve stem 13 is the same size or largerthan the portion of the container 10 housing the agent and the valvestem forms a seal over the portion of the container 10 housing theagent, such that the propellant is directed solely through the portionof the container 10 housing the agent and propellant is prevented fromflowing upwards and allowing the agent to flow upwards out of thecontainer 10 towards the aerosol canister.

In one embodiment, as shown in FIGS. 4 and 5, a swirl chamber 17 orsimilar compartment is located within the body member 2 between thecontainer 10 and the second end 6. The piercing member 12 pierces andpasses through the container 10 and propellant expelled from the aerosolcanister 8 passes through the container 10 and/or through the bypasspathway(s) 15. Propellant and agent travel through the container 10 intothe swirl chamber 17 and propellant from the bypass pathway(s) 15 isdeposited into the swirl chamber 17 where it assists in breaking up theagent and distributing the agent within the propellant. Increasedpassageways, through which additional propellant may flow through, maybe beneficial in some applications because it can provide enhanceddispersement of the agent into the mouth or nose of a user. Preferably,the propellant captures and disperses the agent into the mouth or noseof a user and inhalation by the user directs the agent to the lungs ofthe user.

As shown in FIGS. 9-10, the device may further include an expansionchamber 25 positioned between the aerosol canister 8 and the container10. The propellant housed within the aerosol canister 8 is typically ina liquid state and, as it is expelled from the aerosol canister 8, itexpands to a gaseous state. The expansion chamber 25 may further beincluded in the device to provide a space wherein the propellant mayexpand to a gaseous state before it passes through the container 10 andcaptures the agent.

A nozzle 27 or similar mechanism is located in between the second end 6of the body member 2 and the container 10. The nozzle 27 assists inregulating and directing the flow of the propellant and agent throughthe second end 6 of the body member 2 and into the mouth or nose of theuser. Nozzle 27 includes an orifice 27 a. Orifice 27 a typically willhave a diameter of from about 0.010 to 0.060 inches, preferably 0.012 to0.020 inches. However, dimensions outside these ranges may be useful indelivering particular agents.

The device may further include a sealing mechanism 19 positioned betweenthe aerosol canister 8 and the container 10 for sealing off thepassageway of the propellant expelled from the aerosol canister 8through the container 10 so as to prevent escape of propellant and todirect the propellant through the container 10 and/or bypass pathway(s)15. For example, as shown in FIG. 2, the sealing mechanism 19 may form atunnel-like pathway between the portion of the canister through whichthe propellant is expelled and the container 10. Thus, as the propellantexits the aerosol canister 8, it travels solely through the tunnel-likepathway and through the container 10 thereby eliminating what iscommonly referred to as “blow-by.”

Aerosol canisters are well known and, thus, although described and shownwith reference to a preferred embodiment, the general features (e.g.size, shape, materials) of the aerosol canister 8 may be in accordancewith conventional aerosol canisters.

One embodiment of the aerosol canister 8 is shown in FIG. 3. As shown,the aerosol canister 8 has a valve stem 13 extending from its bottomend. The valve stem 13 may be connected to the aerosol canister 8 via acollar 16 or similar connection mechanism. The valve stem 13 is movablewithin the aerosol canister 8 such that as pressure is applied to thevalve stem 13 in a direction towards the aerosol canister 8, the valvestem 13 is depressed within the aerosol canister 8. This may beaccomplished by, for example, a stop member 9 positioned between theaerosol canister 8 and container 10, such that the aerosol canister 8contacts the stop member 9 as the aerosol canister 8 is moved downwardstowards the container 10. Located through a side wall of the valve stem13 is an aperture 31. When the valve stem 13 is in its normal stateextending out of the aerosol canister 8, as shown in FIG. 8, theaperture 31 is located outside the aerosol canister 8. As pressure isapplied to the valve stem 13 and the valve stem 13 is depressed into theaerosol canister 8, the aperture 31 enters the aerosol canister 8,thereby actuating the aerosol canister 8. Upon actuation, the propellantwithin the aerosol canister 8 is driven out of the aerosol canisterthrough the aperture 31 and through the valve stem 13.

The propellant may be selected from those used in the art such as, forexample, liquid chlorofluorocarbons (CFCs), which includefluorotrichloromethane, dichlorodifluoromethane anddichlorotetrafluoroethane. However, because CFC's are believed to bedestructive of the ozone layer, hydrofluorocarbons (HFCs) such as, forexample, 1,1,1,2-tetrafluoroethane (also commonly referred to aspropellant 134 a, HFC-134 a, and HFA-134 a) and1,1,1,2,3,3,3-heptafluoropropane (also commonly referred to aspropellant 227, HFC-227, and HFA-227), are preferred because they arebelieved to be more ozone friendly than CFC's.

In addition to propellants, the aerosol canister 8, if desired, may alsocontain a variety of agents. For example, the aerosol canister 8 mayfurther house an agent in suspension or solution. The agent insuspension or solution may be, for example, selected from flavoringagents, surfactants, water, alcohol or other solvents, and medicinalagents.

The aerosol canister 8 may be prepared by conventional methods such as,for example, pressure filling or cold filling the propellant into thecanister. Such methods are well known to those skilled in the art.Conventional valves, preferably metering valves, are used to deliver thepropellant of the present invention. Such metering valves deliver aparticular amount of propellant per actuation. Thus, the use of meteringvalves may be desirable to automatically provide the desirable amount ofpropellant required for a particular application. Preferably, theaerosol canister 8 having a metering valve contains an amount ofpropellant for multiple uses.

It is also possible to use other types of valves such as, for example,open flow type valves. Such valves allow for expulsion of the contentsof the can for as long as the valve is depressed. Preferably, because itis possible with such valves to deliver an excessive amount ofpropellant, such aerosol canisters 8 of this form are single-usepressurized containers holding an amount of propellant suitable for asingle use. Thus, after a single use, the aerosol canister 8 is eitherreplaced or the device thrown out.

In a preferred embodiment, the aerosol canister 8 is movable within thebody member 2 towards the container 10 and the piercing member 12 issituated such that, as the aerosol canister 8 is moved towards thecontainer 10, the piercing member 12 likewise moves towards thecontainer 10. For example, the piercing member 12 may be directlymounted to the aerosol canister 8 via the valve stem 13. In anotherembodiment, as shown in FIGS. 1, 2, 7 and 8, a spring 29 and pin 30mechanism connects the piercing member 12 to the valve stem 13. In suchan embodiment, as the aerosol canister 8 is depressed downwards withinthe body member 2 towards the container 10, the spring 29 is compressedand the piercing member 12 pierces and passes through the container 10.The aerosol canister 8 is actuated and propellant is expelled. Then,when the user releases the aerosol canister 8, the spring 29 and pin 30mechanism acts to bring the aerosol canister 8 back upwards in the bodymember 2 to its start position.

In another embodiment, as shown in FIGS. 18 b-e, a stop member 9 ispositioned between the aerosol canister 8 and the container 10 housingthe agent. A spring 60 or similar mechanism is further situated betweenthe stop member 9 and the container 10. The container 10 can be heldwithin the body member 2 by a holding mechanism comprising a lowerportion 20 a and an upper portion 20 b which fit together and which holdthe container 10 as shown in FIGS. 18 b-c. The nozzle 27 is preferablylocated in the lower portion 20 a of the holding mechanism, throughwhich the agent and propellant are expelled from the device. Prior touse, the delivery device 1 is configured as shown in FIG. 18 c, with thevalve stem 14 positioned in the stop member 9 and the spring expanded toseparate the piercing member 12 from the container 10. The device canthen be actuated by pushing the aerosol canister 8 downwards towards thecontainer, as shown in FIG. 18 d. As the aerosol canister 8 is moveddownwards, the stop member 9 is also pushed downwards, therebycompressing the spring 60. The piercing member 12 passes through thecontainer 10 and picks up the agent. As the aerosol canister 8 is movedfurther downwards, the valve stem 14 is pushed upwards into the aerosolcanister 8, as shown in FIG. 18e, thereby actuating the aerosol canister8 to expel propellant. The propellant passes through the piercing member12 (also around the piercing member and/or through bypass pathways 15 insome embodiments), captures and disperses the agent out of the secondend 6 of the device. As shown in FIG. 18e, the lower portion 20 a of theholding mechanism may include a lumen 48 through which the propellantand agent pass and exit through nozzle 27, which directs the propellantand agent through the second end 6.

In one embodiment, the valve stem 13 of the aerosol canister 8 is thepiercing member. Thus, in this embodiment, as the aerosol canister 8 ismoved downwards, the valve stem 13 pierces and passes through thecontainer 10. The valve stem 13 may be hollow such that as the valvestem 13 pierces and passes through the container 10, agent is picked upwithin the valve stem 13. The aerosol canister 8 is then actuated andpropellant is expelled through the hollow valve stem 13, therebycapturing and dispersing the agent out of the valve stem 13 and into themouth or nose of a user. Preferably, in this embodiment, the valve stem13 is designed with a cross section substantially the same as the crosssection of the portion of the container housing the agent, so as tominimize any residue of agent in the container 10. The valve stem 13and/or portion of the container 10 housing the agent may further bedesigned so as to accommodate a precise dose of agent.

Alternatively, it is possible to provide as a piercing member a valvestem 13 with a cross section substantially the same as the cross sectionof the portion of the container 10 housing the agent and a narrow hollowportion such that as the valve stem 13 pierces and passes through thecontainer 10, the agent is pushed through the container 10 rather thanor in addition to being picked up within the valve stem 13. Then, uponactuation of the aerosol canister 8, propellant expelled through thevalve stem 13 contacts and disperses the agent picked up in the valvestem and/or pushed through the container 10 into the mouth or nose of auser.

In some embodiments, wherein the valve stem 13 is the piercing member12, the valve stem 13 can be sharpened at the piercing end to facilitatepiercing of the container 10 and to avoid cutting a piece of thepiercable material free as it pierces and passes through the container10. As set out above, for example, the piercing member, in thisembodiment, the valve stem 13, can be sharpened to about a 30° to 60°angle and blunted at the rim of the piercing member 12 opposite the apexof the point.

The device of the present invention is particularly superior to otherdevices in that it delivers a very high emitted dose of the agent fromthe container 10. As used herein, “emitted dose” is defined as thepercentage of the agent housed in a single dose compartment 22 of thecontainer 10 that is emitted from the device during use.

The exceptionally high emitted dose using the device of the presentinvention is achieved by the present invention by reducing the amount ofresidue that collects and remains in the device. This can beaccomplished in a number of ways.

In some embodiments wherein the mechanism comprises a piercing member 12in the form of a hollow needle, the hollow piercing member 12 has anouter diameter that is approximately the same size as the diameter ofthe compartment 22 housing the agent. This minimizes the amount of agentthat collects between the outer diameter of the piercing member 12 andthe walls of the compartment 22 as the piercing member passes throughand picks up the agent. Further, the thickness of the piercing member 12wall (i.e. the distance between the outer diameter of the hollowpiercing member and the inner diameter of the hollow piercing member) ispreferably minimized so that as the piercing member 12 passes throughthe container 10, most if not all of the agent is picked up inside thehollow of the piercing member 12. Further, any agent not picked upinside the hollow of the piercing member 12 is pushed through thecontainer by the walls of the piercing member. In this embodiment,because the piercing member 12 has an outer diameter that isapproximately the same size as the diameter of the compartment 22housing the agent, approximately all of the agent from the compartment22 is either picked up within the hollow of the piercing member 12 orpushed out of the compartment 22 by the walls of the piercing member.Agent collected between the outer diameter of the piercing member 12 andthe compartment 22 walls is minimized.

Likewise, in some embodiments wherein the mechanism is a solid piercingmember 12, the piercing member 12 has an outer diameter that isapproximately the same size as the diameter of the compartment 22housing the agent. This minimizes the amount of agent that collectsbetween the outer diameter of the piercing member 12 and the compartment22 walls as the piercing member passes through the compartment 22. Asthe solid piercing member 12 passes through the compartment 22,approximately all of the agent is pushed through the compartment towardsthe second end of the device by the piercing member 12. Agent collectedbetween the outer diameter of the piercing member 12 and the compartment22 walls is minimized.

During use, as the piercing member 12 passes through the container 10,it first pierces and passes through the piercable material that sealsthe agent in the container 10. Preferably, the piercable material ispierced but remains connected to the container 10 to prevent thepiercable material from being pushed out of the second end 6 of thedevice into the mouth or nose of the user. The piercable material isdescribed above and, preferably, is formed of one or more thin layers ofmaterial (e.g. polyester, aluminum foil, polyolefin and polypropylene.The thickness of the piercable material is preferably no greater thanabout 0.004 inch, more preferably, between about 0.001 and about 0.003inch, and more preferably, between about 0.001 and about 0.0015 inch. Insome embodiments, to prevent the piercable material from becomingseparated from the container as the piercing member 12 passes through,some clearance space is preferably provided between the piercing member12 and the walls of the compartment 22 housing the agent. This clearancespace allows the piercable material to be pushed up against the wall ofthe compartment 22 by the piercing member 12. If insufficient clearanceis provided, then the piercable material may become separated from thecontainer 10. Thus, a clearance at least as thick as the piercablematerial is preferably provided between the piercing member 12 and theinner walls of the compartment 22. In other words, the piercing member12 is preferably slightly smaller than the diameter of the compartment22 housing the agent by at least the thickness of the piercablematerial. The clearance space can be provided on one side of thepiercing member 12 as it passes through the compartment 22 or it can beprovided on both sides of the piercing member 12. For example, if thepiercable material is 0.001 inch thick, then the piercing member 12could be about 0.001 smaller in diameter than the diameter of thecompartment 22 and the piercing member 22 would be aligned to passthrough the compartment 22 with at least about 0.001 inch clearance onone side of the compartment and approximately no clearance on the otherside of the compartment 22, for example, as shown in FIG. 16 a.Alternatively, for example, if the piercable material is 0.001 thick,then the piercing member 12 could be at least about 0.002 smaller indiameter than the diameter of the compartment 22 and the piercing member12 would be aligned to pass through the center of the compartment 22with at least about 0.001 inch clearance on each side of the compartment22, for example, as shown in FIG. 16 b.

In some of the embodiments, it is desirable to include a guidingmechanism that ensures that the piercing member 12 passes through thecontainer 10 precisely where intended. The guiding mechanism could, forexample, ensure that the piercing member 12 passes precisely through thecenter of the compartment 22 or in any other place within thecompartment. For example, in the embodiment above where the piercablematerial is 0.001 inch thick and the piercing member 12 is at leastabout 0.002 inch smaller in diameter than the diameter of thecompartment 22, the guiding mechanism could ensure that the piercingmember 12 is aligned to pass through the center of the compartment 22with at least 0.001 inch clearance space on each side of the compartment22. In the embodiment above where the piercable material is 0.001 inchthick and piercing member 12 is at least about 0.001 inch smaller indiameter than the diameter of the compartment 22, the guiding mechanismcould ensure that the piercing member 22 is aligned to pass through thecompartment 22 with at least about 0.001 inch clearance space on oneside of the compartment 22 and approximately no clearance on the otherside of the compartment 22.

In one embodiment, the guiding mechanism is in the form of one or morepins 53 and corresponding apertures 54 located within the device, forexample, as shown in FIG. 17. Thus, for example, one or more pins 53 (orapertures) could be located on a portion of the device that movesdownwards as the source of negative pressure and piercing member 12 aremoved downwards and one or more apertures 54 (or pins) could be locatednear the container 10. As the source of negative pressure and piercingmember 12 are moved downwards, the pins 53 will slide into the apertures54 when properly lined up. If the alignment is off, the pins 53 andapertures 54 will prevent further downward movement and will assist inrealigning the device so that the pins 53 and openings 54 line up. In aparticularly preferred embodiment, two pins 53 and two correspondingapertures 54 are located in the device, for example, as shown in FIG.17, for aligning the piercing member 12 to pass through the properportion of the container 10.

The amount of residue that is collected and remains within thecompartment 22 after use, e.g. along the side walls of the compartment22, can be further eliminated by providing an aerosol canister thatexpels propellant not only through the hollow piercing member 12 butalso through the compartment 22 around the piercing member 12.

In some embodiments, the amount of residue that is collected and remainsin the device is further reduced by designing the second end 6(“mouthpiece”) accordingly. In general, the second end 6 is designed toinhibit collection of residue along the surfaces. For example, in someembodiments, the second end 6 through which the agent and propellantexit the device and enter the user's mouth is enlarged. When thepropellant and agent exit the second end 6, the stream of the propellantand agent is believed to expand into a generally conical-like shape.Thus, by forming the second end 6 to prevent impingement of thepropellant and agent against the inner walls of the second end 6,collection and residue can be minimized. This can be done, for example,by forming the sides of the second end 6 to flared outwards, forexample, as shown in FIG. 18

The collection of residue in the device is further minimized byeliminating potential surfaces and crevices within the device where theagent can collect. In one preferred embodiment shown in FIG. 20,accumulation is reduced by having piercing member 12 stop just above acurved surface 58 that sweeps down towards nozzle 27 as shown in FIG. 20c. This is also shown in FIG. 18.

Further, when the piercing member 12 is passed through the container 10and the propellant expelled to drive the agent through the second end 6,the piercing member 12 is preferably positioned at the top of the radiusof curved surface 58, as shown in FIG. 20. This further minimizes thecollection of agent within the inner surfaces of the device.

In the device shown in FIG. 20, the drawer-like member is provided witha guiding mechanism in the form of one or more pins 53 and correspondingstructure, e.g., apertures 54 shown in FIG. 2 la to accept pins 53.Similar to the embodiment shown in FIG. 17, pins 53 pass through notches53 a in the drawer on either side of the container in order to perfectlyalign the passage of piercing member 12 through the aperture and therebycapture the maximum amount of agent. Guide pins 53 are longer than theneedle, so that pins 53 pass through notches 53 a to sufficiently securedrawer 40 before piercing member 12 passes through container 10 indrawer-like member 40. Piercing member 12 thus stops at radius 58 asshown in FIG. 20 c, thereby centralizing piercing member 12 with greataccuracy and thereby maximizing capture of the agent.

The collection of residue in the device can further be reduced byproviding piercing member 12 or other mechanism with a beveled tip, asshown in FIG. 1, wherein the beveled tip is positioned to face the exitthrough which the propellant and agent exit the second end 6. This willdirect the propellant and agent through the exit of the second end 6 sothat the agent and propellant does not impinge on the inner surfaces ofthe second end 6.

Still further, collection of residue in the device is further minimizedby providing highly polished inner surfaces of molded parts forming thedevice as opposed to machined surfaces.

The present device is capable of delivering particularly a highrespirable fraction of agent. As used herein, the respirable fraction isthe percentage of the dose that is delivered to the lungs. With priordelivery devices, a respirable fraction of less than 30% was possible.However, with the present invention, respirable fractions of greaterthan 30%, more preferably, greater than 35%, more preferably, greaterthan 40%, more preferably, greater than 45%, more preferably, greaterthan 50%, more preferably, greater than 60%, more preferably, greaterthan 65%, more preferably, greater than 70%, more preferably, greaterthan 75%, more preferably, greater than 80%, and even greater than 85%can be achieved.

The use of the delivery device 1 of the present invention can be furtherunderstood from the following discussion relating to a method fortreating bronchial asthma and with reference to FIGS. 1-10.

To operate the device, a user places the second end 6 of the device nearthe bodily site. For example, when used to deliver the agent to themouth or nose, the user inserts the second end 6 of the device into themouth or nose. The user then presses the aerosol canister 8 downwardstowards the container 10 within the body member 2 until the piercingmember 12 pierces and passes through the container 10, thereby pickingup and carrying the agent towards the second end 6 of the device. Theaerosol canister 8 is actuated to expel propellant through the bodymember 2 towards the second end 6. The expelled propellant captures anddisperses the agent into the mouth or nose of the user. During use, thepropellant captures and disperses the agent into the mouth or nose ofthe user and inhalation by the user directs the agent to the lungs. Whenused to deliver the agent to other bodily sites, for example, to the earof a user, the device is used as described above, without the user'sinhalation to direct the agent.

The present invention also includes kits that comprise one or moredelivery device 1 of the invention. Kits of the invention also may beinclude one or more containers 10 and aerosol canister 8 for use withthe delivery device 1, and/or written instructions for use of thedelivery device 1 and other components of the kit.

The delivery device 1 and methods of use of the present invention willbe further illustrated with reference to the following Examples whichare intended to aid in the understanding of the present invention, butwhich are not to be construed as a limitation thereof.

All documents mentioned herein are incorporated by reference herein intheir entirety.

EXAMPLES

A number of tests were performed to analyze the dispersement of thepropellant and agent out of the second end of the device. In thesetests, the delivery device of the present invention was used to deliverthe propellant with dispersed agent into a “black box” shown in FIG. 19.The black box comprises an elongate box approximately 2 feet long, 1.0foot high and 1.0 foot wide. The black box has, at one end of itslength, an opening through which the second end 6 of the device isinserted. Along the front of the black box is a short wall shielding aseries of eight to ten lights from the camera lens and highlighting thepowder stream discharged into the box. A camera on a tripod operatingat, for example, approximately 300 frames/second, in some cases 3000frames/second takes snapshots of the interior of the black box. Thedevice of the present invention is actuated to dispel propellant andagent through the opening in the black box as the camera takes snapshotsof the interior of the black box.

In each of the tests, the propellant with dispersed agent exits thesecond end 6 of the present device in the form of a soft, low velocitycloud. Further, when the device is used to deliver the propellant withdispersed agent into a large open space, e.g. a room, that is well lit,the propellant with dispersed agent exits the second end 6 of thepresent device in the form of a soft, low velocity cloud that remainssuspended and remains visible for greater than about 3 seconds postactuation.

Without being bound by theory, it is believed that the suspension of themixture by the present device provides a higher respirable fraction ofagent. With prior devices, for example, the propellant and agent mixtureis expelled from the devices in a high velocity, liner stream. This highvelocity, linear stream impinges on the back of the mouth and throat ofthe user. With the present device, on the other hand, the mixture isdelivered to the mouth in a soft, low velocity, cloud-like formationthat remains suspended as the user inhales and directs the mixture downthe throat to the treatment area (e.g. lungs).

The foregoing description of the invention is merely illustrativethereof, and it is understood that variations and modifications can beeffected without departing from the scope or spirit of the invention asset forth in the following claims.

1-71. (canceled)
 72. A device for delivery of two or more agentscomprising: a body member having at a first end a canister housing apropellant and a second end adapted for insertion into the mouth or noseof a user; a container within the body member positioned between thecanister and the second end; the container housing two or more agents,wherein the two or more agents are separated from each other withpiercable material; a mechanism for exposing the agents in the containerto the propellant, the mechanism positioned between the canister and thecontainer; whereby as the canister is moved towards the container, themechanism exposes the two or more agents in the container to thepropellant and the canister is actuated to expel the propellant andagents into the mouth or nose of the user.
 73. The device of claim 72wherein the container comprises one or more compartments, eachcompartment being sealed at a bottom and top end with a piercablematerial, each compartment housing the two or more agents.
 74. Thedevice of claim 73 wherein the compartments house two or more agents inlayers, the layers being separated from each other with piercablematerial.
 75. The device of claim 72 wherein the canister further housesa dose of agent in suspension or solution.
 76. The device of claim 75wherein the dose of agent is selected from flavoring agents,surfactants, water, alcohol or other solvents, and medicinal agents. 77.The device of claim 72 wherein the mechanism passes through thecontainer thereby carrying the agents towards the second end.
 78. Thedevice of claim 77 wherein the mechanism is sized to carry precise dosesof agents to the second end.
 79. The device of claim 77 wherein the sizeof the mechanism controls the doses of agents delivered by the device.80. The device of claim 72 wherein the mechanism is a piercing member.81. The device of claim 80 whereby as the canister is moved towards thecontainer, the piercing member passes through the container, therebycarrying the agents towards the second end.
 82. The device of claim 80wherein at least the tip portion of the piercing member is hollow andthe agents are picked up within the hollow portion of the piercingmember.
 83. The device of claim 82 wherein the inner diameter of thepiercing member is sized to pick up precise doses of the agents.
 84. Thedevice of claim 82 wherein the size of the inner diameter of thepiercing member controls the doses of agents delivered by the device.85. The device of claim 80 wherein the piercing member is a blade orblade-like member.
 86. The device of claim 72 wherein the propellant isa chlorofluorocarbon or hydrofluoroalkane propellant.
 87. The device ofclaim 72 wherein the propellant is selected from hydrofluoroalkane 134 aand hydrofluoroalkane
 227. 88. The device of claim 72 wherein thecanister includes a valve stem through which propellant is expelled, andwherein the valve stem comprises the mechanism.
 89. The device of claim74 wherein the mechanism comprises a piercing member and wherein thepiercing member passes through the piercable material at the top end ofthe container, passes through the layers of agents and piercablematerial separating the layers of agents, and passes through thepiercable material at the bottom end thereby carrying the agents towardsthe second end.
 90. A device for delivery of an agent for treatingdiabetes comprising: a body member having at a first end a canisterhousing a propellant and a second end adapted for insertion into themouth or nose of a user; and a container within the body member, forholding an agent effective in treating diabetes, wherein the containeris positioned between the canister and second end; whereby as thecanister is moved towards the container, the canister is actuated toexpel the propellant and agent into the mouth of a user, whereby devicedelivers a respirable fraction of agent that is effective in treatingdiabetes.
 91. A device for delivery of an agent comprising: a bodymember having at a first end a canister housing a propellant and asecond end adapted for insertion into the mouth or nose of a user; and acontainer within the body member, for holding the agent, wherein thecontainer is positioned between the canister and second end; whereby asthe canister is moved towards the container, the canister is actuated toexpel the propellant and agent into the mouth or nose of the user, andwherein the device delivers a respirable fraction of agent of at leastabout 60%.
 92. The device of claim 91 wherein the respirable fraction isat least about 65%.
 93. The device of claim 91 wherein the respirablefraction is at least about 70%.
 94. The device of claim 91 wherein therespirable fraction is at least about 75%.
 95. The device of claim 91wherein the respirable fraction is at least about 80%.
 96. The device ofclaim 91 wherein the respirable fraction is at least about 85%.